Investigation of Some Inhibitors of Alzheimer Associated Amyloid Beta Aggregation by Quantum Optimization and Molecular Docking Simulation

Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to the death of braincells and cognitive decline. Aggregation of extracellular amyloid plaque containing amyloid β-peptide (Aβ) and intracellular neurofibrillary tangles containing tau protein is two main causes ofAlzheimer s disease [1]. The most abundant forms of Aβ are the Aβ1–40 and Aβ1–42. Aβ42 ismore prone to self-assemble and therefore more toxic than Aβ40B [2]. This study is a report ofquantum mechanics-guided ligand optimization and docking of six plant-based compoundsagainst two forms of Aβ42 (PDB ID: 2BEG and 2MXU). The three-dimensional (3D) structuresof the ligands were built and their geometries were optimized through Gaussian 09W. Themolecular docking and 2D ligand interactions were conducted by Molsoft ICM-Pro 3.8-6a. Theresults indicated that binding to the 2BEG fibril was more desirable than to 2MXU. Dockingresults show that the semi-empirical binding energy (ICM score) between Curcumin, RosmarinicAcid, Apigenin, Quercetin, Melatonin, O-vanillin with 2BEG are about to -26.07, -22.39, -21.05,-20.82, -16.57, -15.35 kcal/mol, respectively. Among them, curcumin represents more stableinteraction energy (-26.07). The most important interaction is hydrogen bond that is formedbetween O of CO with G37 in a distance around 2.634 Å and another between H of OH with L17which had 3.178 Å length.